Absence of Putative Artemisinin Resistance Mutations Among Plasmodium falciparum in Sub-Saharan Africa: A Molecular Epidemiologic Study
Steve M. Taylor,Steve M. Taylor,Christian M. Parobek,Derrick K. DeConti,Kassoum Kayentao,Sheick Oumar Coulibaly,Brian Greenwood,Harry Tagbor,John V. Williams,Kalifa Bojang,Fanta Njie,Meghna Desai,Simon Kariuki,Julie Gutman,Don P. Mathanga,Andreas Mårtensson,Billy Ngasala,Melissa D. Conrad,Philip J. Rosenthal,Antoinette Tshefu,Ann M. Moormann,John M. Vulule,Ogobara K. Doumbo,Feiko O. ter Kuile,Feiko O. ter Kuile,Steven R. Meshnick,Jeffrey A. Bailey,Jonathan J. Juliano +27 more
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TLDR
An assay to quantify rare polymorphisms in parasite populations that uses a pooled deep-sequencing approach to score allele frequencies is developed and validated by evaluating mixtures of laboratory parasite strains, and used to screen P. falciparum parasites from >1100 African infections collected since 2002.Abstract:
Plasmodium falciparum parasites that are resistant to artemisinins have been detected in Southeast Asia. Resistance is associated with several polymorphisms in the parasite's K13-propeller gene. The molecular epidemiology of these artemisinin resistance genotypes in African parasite populations is unknown. We developed an assay to quantify rare polymorphisms in parasite populations that uses a pooled deep-sequencing approach to score allele frequencies, validated it by evaluating mixtures of laboratory parasite strains, and then used it to screen P. falciparum parasites from >1100 African infections collected since 2002 from 14 sites across sub-Saharan Africa. We found no mutations in African parasite populations that are associated with artemisinin resistance in Southeast Asian parasites. However, we observed 15 coding mutations, including 12 novel mutations, and limited allele sharing between parasite populations, consistent with a large reservoir of naturally occurring K13-propeller variation. Although polymorphisms associated with artemisinin resistance in P. falciparum in Southeast Asia are not prevalent in sub-Saharan Africa, numerous K13-propeller coding polymorphisms circulate in Africa. Although their distributions do not support a widespread selective sweep for an artemisinin-resistant phenotype, the impact of these mutations on artemisinin susceptibility is unknown and will require further characterization. Rapid, scalable molecular surveillance offers a useful adjunct in tracking and containing artemisinin resistance.read more
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Journal ArticleDOI
[Plasmodium falciparum resistance to artemisinin-based combination therapies (ACTs): Fears of widespread drug resistance].
TL;DR: It is essential to better understand, from phenotypic and genotypic points of view, the mechanisms of resistance developed by the parasite Plasmodium falciparum face artemisinin and its derivatives in order to offer new therapeutic tools.
Dissertation
Genetic basis of resistance in Plasmodium falciparum parasites exposed to pure artemisinin and Artemisia annua extracts
TL;DR: .................................................................................................................. xvi CHAPTER One ..............................................................................................................
Altered Intraerythrocytic Development Phenotypes of Artemisinin-Resistant Plasmodium falciparum Confer a Fitness Advantage
TL;DR: Novel phenotypic resistance traits expressed by artemisinin-resistant Plasmodium falciparum are described and insights are offered into a novel mechanism of drug resistance in P. falcIParum and new tools for monitoring the spread of art Artemisinin resistance are offered.
Dissertation
Drug Development in Dengue Virus and Molecular Epidemiology of Malaria in Western
TL;DR: An abstract of a dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Department of Molecular Genetics and Microbiology in the Graduate School of Duke University 2017 is submitted.
Posted ContentDOI
High-resolution micro-epidemiology of parasite spatial and temporal dynamics in a high malaria transmission setting in Kenya
Cody S. Nelson,Kelsey M. Sumner,Kelsey M. Sumner,Elizabeth Freedman,Joseph W. Saelens,Andrew Obala,Judith N. Mangeni,Steve M. Taylor,Steve M. Taylor,Wendy Prudhomme O’Meara +9 more
TL;DR: Findings of both micro- and macro-scale organization of parasite populations might be harnessed to inform next-generation malaria control measures and to identify the molecular signature of an outbreak.
References
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